α-Methyltryptophan

Clinical data
Other names	αMTP; α-MTP; AMTP; α-Methyl-L-tryptophan;alpha-Methyltryptophan;alpha-Methyl-L-tryptophan
Drug class	Serotonin receptor agonist
Identifiers
IUPAC name (2S)-2-amino-3-(1H-indol-3-yl)-2-methylpropanoic acid
CAS Number	16709-25-4
PubChemCID	676155
ChemSpider	588899
UNII	1F33TJ4ZOP
CompTox Dashboard(EPA)	DTXSID60350250
Chemical and physical data
Formula	C12H14N2O2
Molar mass	218.256 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@](CC1=CNC2=CC=CC=C21)(C(=O)O)N
InChI InChI=1S/C12H14N2O2/c1-12(13,11(15)16)6-8-7-14-10-5-3-2-4-9(8)10/h2-5,7,14H,6,13H2,1H3,(H,15,16)/t12-/m0/s1 Key:ZTTWHZHBPDYSQB-LBPRGKRZSA-N

α-Methyltryptophan (αMTP orα-MTP) is asynthetictryptaminederivative, an artificialamino acid, and aprodrug ofα-methylserotonin (αMS).^[1][2][3] It is the α-methylatedderivative oftryptophan, while αMS is the α-methylatedanalogue ofserotonin.^[1][3] αMTP has been suggested for potential therapeutic use in the treatment of conditions thought by some authors to be related to serotonin deficiency, such asdepression.^[1] Inlabeled forms, αMTP is also used as aradiotracer inpositron emission tomography (PET)imaging to assess serotoninsynthesis and certain other processes.^{[4][2][5][6][7]}

αMS is anon-selectiveserotonin receptor agonist, including of the serotonin5-HT₂ receptors, and has been described as a "substitute neurotransmitter" of serotonin.^{[1][8][9][10]} However, whereas αMS itself is toohydrophilic to efficiently cross theblood–brain barrier, thus beingperipherally selective, αMTP is able to cross the blood–brain barrier and, followingtransformation, deliver αMS into the brain.^[1][4]

Besides αMS, αMTP is alsometabolized intoα-methyltryptamine (αMT).^[11][12] αMT is aserotonin–norepinephrine–dopamine releasing agent, a non-selective serotonin receptor agonist, and aserotonergic psychedelic.^[13][14] However, αMT levels are much lower than those of αMS with αMTP and αMT is described as a minor metabolite of αMTP.^[11][12] In accordance, the behavioral effects of αMTP and αMT in animals are described as strikingly different.^[12]α-Methylmelatonin can also be formed in small amounts from αMTP, but the formation of this compound with αMTPin vivo appears to be negligible.^[15]

αMTP and αMS remain in the body for long amounts of time following a single dose of αMTP, whereastryptophan results in only a short-lasting increase in brainserotonin levels.^[1][5] This is attributed to the resistance tometabolism of these compounds afforded by their α-methyl group.^[1] As such, αMTP might be advantageous for therapeutic purposes relative to tryptophan.^[1] αMTP is useful over tryptophan in PET imaging because αMTP, unlike tryptophan, is not incorporated as anamino acid into brainproteins, and because, unlike serotonin, αMS is not asubstrate formonoamine oxidase (MAO) and hence remains in the brain for a much longer amount of time.^[3][4][5] The preceding limitations of tryptophan make its use in PET imaging in humans impossible, whereas αMTP is a viable agent for such purposes.^[5]

αMTP is first converted bytryptophan hydroxylase intoα-methyl-5-hydroxytryptophan (αM-5-HTP or α-methyl-5-HTP), the α-methylated analogue of5-hydroxytryptophan (5-HTP), prior to beingdecarboxylated byaromaticL-amino acid decarboxylase (AAAD) into αMS.^[1][4][3][5] αM-5-HTP has also been suggested for potential therapeutic use.^[1] However, αM-5-HTP is also atyrosine hydroxylaseinhibitor similarly toα-methyltyrosine, as well as an AAAD inhibitor, and has been found todeplete levels of brainnorepinephrine in animals, although not levels of braindopamine.^{[1][16][17][18]}

• O-Acetylbufotenine (O-acetyl-N,N-dimethylserotonin)
• α-Methylphenylalanine
• Metirosine (α-methyltyrosine)
• Methyldopa (α-methyl-DOPA)
• Neurotransmitter prodrug

• Alpha-Alkyltryptamines
• Alpha-Amino acids
• Prodrugs
• Serotonin receptor agonists

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